The experiments described in this proposal are directed to determining the mechanism(s) of prevention of leukemia induction by 334C murine leukemia virus, other leukemia viruses, and agents which may "activate" C-type RNA virus(es) in the treated animal (total-body X- irradiation, chemical carcinogens, graft-versus-host reaction), in a murine model system in which "protective factors(s)" are transmitted via the milk from 334C virus-immunized mothers to their offspring (offspring are "protected" against leukemia development following challenge at birth with 334C virus). In vivo and in vitro studies will be carried out to identify the nature of the "protective factor(s)". These studies will include use of the XC-cell assay for infectious murine leukemia virus to determine the in vitro virus-neutralizing capabilities of preparation of milk and sera from virus-immunized mice, as well as separation of the major classes of immunoglobulins and their identification utilizing immunoelectrophoresis and radioimmunodiffusion techniques. The role of humoral vs. cell-mediated cytotoxic immunity will be explored. An integral part of these studies will be the purification and quantitation of virus preparations in terms of infectivity, and the development of more effective virus-immunizing preparations and immunization procedures.